大黄对大鼠肝再生过程中cyclinD_1影响的实验研究

[目的]探讨大黄对大鼠肝再生过程中cyclin D1的影响。[方法]将24只Wistar大鼠随机分为4组,分别为对照组、模型组、大黄组和促肝细胞生长素(pHGF)组,每组6只。模型组、大黄组和pHGF组大鼠切除肝脏左叶和中叶,对照组仅切开腹腔翻动肝左叶和中叶。大黄组和pHGF组于实验前3 d至实验结束,分别腹腔注射大黄1 ml/100g和pHGF 1 ml/100 g,每日1次。术后48 h处死大鼠,应用逆转录聚合酶链反应法检测大鼠肝组织cy-clinD1 mRNA的表达。[结果]与对照组比较,模型组、大黄组和pHGF组大鼠肝组织cyclinD1 mRNA表达均显著升高(P0.01);与模型组比较,大黄组和pHGF组大鼠肝组织cyclinD1 mRNA表达均显著升高(P0.01),大黄组和pHGF组大鼠肝组织cyclinD1 mRNA表达差异无统计学意义(P0.05)。[结论]大黄显著促进cyclinD1 mR-NA表达,从而促进肝部分切除术后大鼠的肝再生。     

灯盏花素干预大鼠肝星状细胞TGFβ1、α-SMA的表达

目的 研究灯盏花素对CCl4诱导的肝纤维化模型大鼠TGFβ1、α-SMA表达的研究.方法 本实验用CCl4诱导大鼠肝纤维化模型,喂服灯盏花素.60只Wistar大鼠随机分为正常对照组、模型组、灯盏花素高剂量组、灯盏花素中剂量组、灯盏花素低剂量组、秋水仙碱组.用药4w后,测定肝纤维化模型大鼠的谷草转氨酶、谷丙转氨酶,检测平滑肌肌动蛋白mRNA和蛋白的表达,转化生长因子mRNA与蛋白的表达.结果 模型组大鼠血清ALT、AST明显高于正常对照组(P＜0.05).与模型组相比较,灯盏花素高、中、低剂量组ALT、AST均明显降低(P＜0.05).模型组与正常对照组α-SMA mRNA及蛋白有显著性差异(P＜0.01);灯盏花素不同剂量组均能使α-SMA mRNA及蛋白表达显著降低(P＜0.01).模型组与正常对照组TGFβ1 mRNA及蛋白有显著性差异(P＜0.01),灯盏花素不同剂量组均能使TGFβ1 mRNA及蛋白的表达显著降低(P＜0.01或P＜0.05).光镜显示:灯盏花素各剂量组的肝脏病理学改变较模型组减轻.结论 ①灯盏花素能保护肝细胞活性,促进肝细胞修复再生;降低转氨酶,具有抗肝纤维化作用.②灯盏花素可以降低α-SMA、TGFβ1表达,抑制星状细胞激活.     

姜黄素抑制肝星状细胞MyD88及信号通路细胞因子表达的研究

目的探讨姜黄素在肝星状细胞MyD88依赖性途径中的作用机制。方法体外培养大鼠肝星状细胞株HSC-T6,将HSCT6分为空白对照组、Control siRNA组、MyD88 siRNA干扰组、姜黄素组、姜黄素+Control siRNA组、姜黄素+MyD88 siRNA干扰组,siRNA处理组给予siRNA干扰48 h后,姜黄素组加入姜黄素作用24 h,各组均在收集细胞前12 h给予LPS诱导,收集各组细胞,Western blotting法检测MyD88蛋白表达;RT-PCR术检测细胞因子mRNA的表达。结果 MyD88 siRNA干扰、姜黄素均可降低MyD88蛋白的表达(P0.05),同时给予MyD88 siRNA干扰和姜黄素作用时,MyD88蛋白下降更明显(P0.05)。MyD88 siRNA干扰后TLR2、TLR4 mRNA表达差异无统计学意义(P0.05),姜黄素作用后TLR2、TLR4的mRNA表达降低,二者同时作用其下降更显著(P0.05);MyD88 siRNA干扰、姜黄素处理后NF-κB、TNF-α、IL-1βmRNA表达均降低,二者同时作用后其下降更明显(P0.05)。结论姜黄素可能通过抑制MyD88蛋白表达和MyD88依赖途径上的多种细胞因子的mRNA表达而阻断MyD88依赖性信号通路的转导,促进活化的HSCs凋亡,从而发挥其抗肝纤维化的作用。     

Notch/Jagged信号在肝部分切除后肝再生中的表达

目的研究Notch/Jagged信号传导通路在大鼠肝部分切除术后肝再生中所起的作用。方法取雌性wister大鼠行肝部分切除术,术后0 min、5 min、15 min、30 min、1 h、3 h、6 h、12 h、1 d、2 d、4 d、7 d留取再生肝组织,观察大体组织变化,检测Notch-1和Jagged-1蛋白的表达,并通过RT-PCR检测Notch-1和Jagged-1的mRNA的表达。结果再生肝Notch-1蛋白第2 d在门脉周围细胞表达增强,第4 d在肝血窦内皮细胞表达增强,Jagged-1在正常肝脏标本中在胆管分布,在肝细胞也有少量表达。在再生的肝上,第2 d在门脉周围的肝细胞上较强地表达,第4 d在胆管内皮细胞表达增强。Notch-1的mRNA表达量在6 h-2 d下调,Jagged-1的mRNA表达量在3-6 h上调,12 h-2 d下调,4 d恢复。统计学处理采用方差分析方法、t检验及直线相关方法（P〈0.05）。结论Notch/Jagged信号通路的激活在肝再生中扮演着重要的角色。它可以促进胆管的形成和结构维持,有助于新生血管的形成及肝细胞的增殖。     

AMPK激动剂预处理对肝缺血再灌注损伤大鼠模型的影响及相关机制

目的初步探讨腺苷酸活化蛋白激酶(AMPK)激动剂预处理对大鼠肝缺血再灌注损伤大鼠模型的影响及可能机制。方法 54只健康SPF级SD雄性大鼠随机平均分为3组。5-氨基咪唑-4-甲酰胺核苷酸(AICAR)组(实验组)、缺血再灌注组(对照组)和假手术组,每组18只。每组分别于肝缺血再灌注术后12、24、72 h取材,检测ALT、AST、TBil、TNFα和IL-6浓度,肝三磷酸腺苷(ATP)水平,HE染色观察肝组织学变化,实时荧光定量PCR检测AMPK、哺乳动物雷帕霉素靶蛋白(mTOR)、葡萄糖转运蛋白4型(GLUT4)、多药耐药蛋白2(MRP2)的mRNA相对表达水平,Western Blot检测磷酸化AMPK、磷酸化mTOR、磷酸化GLUT4、MRP2的蛋白表达水平。多组间比较采用重复测量资料的方差分析,进一步两两比较采用LSD-t检验。结果 HE染色结果显示,实验组肝损伤程度在各时点都较对照组轻。术后12、24、72 h,对照组血清ALT、AST、TBil、IL-6、TNFα均高于实验组和假手术组,而实验组均高于假手术组(P值均0.05)。术后12、24、72 h,实验组肝组织ATP水平均高于对照组和假手术组,而对照组均低于假手术组(P值均0.05)。术后12、24、72 h,实验组AMPK、GLUT4、MRP2 mRNA相对表达水平及磷酸化AMPK、磷酸化GLUT4、MRP2蛋白表达水平均高于对照组和假手术组(P值均0.05);对照组AMPK mRNA相对表达水平及磷酸化AMPK蛋白表达水平均高于假手术组,而GLUT4、MRP2 mRNA相对表达水平及磷酸化GLUT4、MRP2蛋白表达水平均低于假手术组(P值均0.05)。实验组mTOR mRNA相对表达水平及其磷酸化mTOR蛋白表达水平均低于对照组和假手术组(P值均0.05);对照组mTOR mRNA相对表达水平及其磷酸化mTOR蛋白表达水平均高于假手术组(P值均0.05)。结论 AICAR预处理能激活AMPK信号通路,改善能量代谢途径,减轻肝脏炎症反应,从而降低肝缺血再灌注损伤程度。     

非酒精性脂肪肝大鼠部分肝切除术后肝再生功能的变化

目的 探讨大鼠非酒精性脂肪肝（NAFLD）部分肝脏切除术后肝再生功能的变化。方法 80只Wistar大鼠，随机分为正常对照组（C组，35只）与NAFLD组（F组，45只），C组给予正常饮食喂养，F组给予高脂饲料喂养。在喂养至第12周时行70％肝切除术，两组动物分别于术后0、1、12、24、36h处死，取出残肝，计算再生肝重比；光镜下计数核分裂肝细胞；透射电镜观察术后肝细胞超微结构的变化；免疫组织化学染色法检测增殖细胞核抗原阳性表达率；半定量逆转录聚合酶链反应检测细胞周期蛋白D1的表达变化。结果 光镜和电镜观察显示F组肝窦狭窄迂曲，细胞质内大量脂滴沉积，细胞核小，细胞器少，能量代谢及细胞增殖均不活跃。F组术后12、24、36h核分裂相计数明显低于C组同时相点（P〈0．01）；F组术后再生肝重比、S期细胞分数及增殖指数也较C组下降，差异有统计学意义（P〈0．01）；F组增殖细胞核抗原阳性率、细胞周期蛋白D1的mRNA表达在术后12、24、36h均明显低于C组同时相点（P〈0．01）。结论 中至重度NAFLD大鼠部分肝切除术后DNA合成高峰滞后，肝再生延迟，再生进程主要被阻滞在细胞周期的G1／S期调控点。     

早期生长反应因子1信号通路在大鼠急性肝内胆汁淤积性肝损伤中的作用

目的 探讨早期生长反应因子1(Egr-1)信号通路在大鼠急性肝内胆汁淤积性肝损伤中的作用.方法 α-异硫氰酸萘酯50 mg/kg一次灌胃建立大鼠急性肝内胆汁淤积性肝损伤模型,实时荧光定量PCR检测灌胃后24、48、72 h肝组织中Egr-1、细胞因子诱导的中性粒细胞趋化因子1和巨噬细胞炎症蛋白2 mRNA表达量,免疫组织化学法检测诱导型一氧化氮合酶蛋白表达,双抗体夹心酶联免疫吸附法检测肝组织匀浆上清液中肿瘤坏死因子α和白细胞介素6含量,硫代巴比妥酸比色法、黄嘌呤氧化酶法和硝酸还原酶法分别检测肝组织匀浆上清液中丙二醛、超氧化物歧化酶和一氧化氮含量,比色法检测肝组织中髓过氧化物酶含量.结果 24、48、72 h模型组肝组织中,中性粒细胞趋化因子1和巨噬细胞炎症蛋白2 mRNA表达量均高于对照组(P值均＜0.05),24、48 h模型组肝组织中Egr-1 mRNA表达量均高于对照组(P值均＜0.05),72 h模型组肝组织Egr-1 mRNA表达量与对照组的差异无统计学意义(P＞0.05);3个时间点模型组肝组织一氧化氮合酶吸光度值均低于对照组(P值均＜0.05),肿瘤坏死因子α、白细胞介素6、髓过氧化物酶、丙二醛均高于对照组(P值均＜0.05),一氧化氮、超氧化物歧化酶则低于对照组(P值均＜0.05).结论 肝内胆汁淤积性肝损伤存在以Egr-1为起始因子的信号传导通路,从而引起肝细胞损伤.诱导型一氧化氮合酶和一氧化氮在肝内胆汁淤积性肝损伤信号通路中可能发挥保护作用.     

胆酸对大鼠肝部分切除术后肝细胞脂质代谢及法尼醇X受体表达的影响

目的探讨胆酸对肝细胞脂质代谢、法尼醇X受体(FXR)及肝再生的影响。方法建立部分肝切除大鼠模型,随机分成3组:G1组(正常喂养),G2组(给予0.2%胆酸喂养),G3组(正常饮食中加入50%葡萄糖),每组10只,喂养后7 d切除大鼠70%肝组织,于术后72 h取出肝组织及血液标本,检测相关指标。RT-PCR和Western印迹检测SHP、CYP7A1、BSEP的表达;试剂盒检测肝细胞中甘油三酯、胆固醇的水平。结果与G1相比,G2组小异二聚体伴侣(SHP)、胆盐输出泵(BSEP)表达显著升高(P0.05),胆固醇7α-羟化醇(CYP7A1)表达显著降低(P0.05);G3组SHP、BSEP表达略增高(P0.05),CYP7A1显著升高(P0.05)。G2组甘油三酯(TG)水平显著降低,胆固醇(TC)含量显著升高,而G3组TG略升高,TC含量降低(均P0.05)。结论胆酸可促进肝细胞再生,FXR在调控肝细胞代谢中发挥重要作用。     

大鼠肝部分切除后PGE_2对肝再生的作用及TGF-αmRNA在肝细胞再生过程中的表达

本实验分组观察了前列腺素E_2(PGE_2)于不同时间注射对肝部分切除大鼠肝细胞再生的作用.同时测定了再生肝组织内转导生长因子α(TGF-α)mRNA的表达.结果发现,肝部分切除大鼠术前30分钟给予PGE_2,具有促进肝细胞再生的作用,其DNA合成率与对照组相比高1.5倍.而术后30分钟及12小时给药则无此作用.再生肝细胞内,TGF-αmRNA明显高于正常肝组织.本文结论:术前给予PGE_2具有启动和加速肝再生的作用.同时,TGF-α在肝再生过程中也具有相当重要的作用.     

STAT3在对乙酰氨基酚所致小鼠肝损伤后肝细胞再生中的作用

目的探讨STAT3在对乙酰氨基酚(APAP)致小鼠肝细胞损伤后肝细胞增殖中的作用。方法体外培养小鼠正常肝细胞AML12,APAP(1、2.5、5、10、20 mmol/L)刺激12、24或48 h,等体积PBS作为对照组。筛选出最佳刺激浓度和作用时间后,AG490(10、50、100μmol/L)作用AML12。CCK8法检测AML12细胞活力。RT-PCR检测AML12中PCNA、CyclinD1、Ki67的mRNA表达水平。Western Blot法检测STAT3、p-STAT3及PCNA、CyclinD1表达水平。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果APAP作用24 h及48 h后,与对照组比较,各浓度组AML12细胞活力均降低(P值均<0.05);APAP浓度为2.5 mmol/L时,细胞活力分别为0.717±0.027、0.752±0.014,与对照组比较差异均有统计学意义(P值均<0.05),能够满足后续实验条件。与对照组比较,24 h APAP(2.5 mmol/L)组PCNA、CyclinD1及Ki67 mRNA的表达均降低(P值均<0.01);与24 h APAP组比较,48 h APAP(2.5 mmol/L)组PCNA、CyclinD1及Ki67 mRNA的表达均升高(P<0.01),因此选择APAP 2.5 mmol/L、刺激时间48 h来模拟体外损伤AML12细胞后肝细胞再生的模型。加入AG490,与对照组比较,10、50μmol/L AG490组细胞活力变化无统计学意义,余各组细胞活力均降低(P值均<0.01);与APAP组比较,AG490(50μmol/L)+APAP组和AG490(100μmol/L)+APAP组细胞活力降低(P值均<0.01),因此选择50μmol/L AG490作为后续实验处理浓度。与对照组比较,APAP组p-STAT3的蛋白水平升高(P<0.01),而AG490组、APAP+AG490组降低(P值均<0.05);与APAP组比较,APAP+AG490组PCNA、CyclinD1蛋白水平及PCNA、CyclinD1、Ki67 mRNA表达均降低(P值均<0.05)。结论STAT3参与APAP诱导小鼠肝细胞损伤后的细胞增殖,而AG490作为STAT3抑制剂通过抑制STAT3磷酸化从而抑制APAP肝损伤后肝细胞增殖。     

Expressions of molecules associated with hepatocyte growth factor activation after hepatectomy in liver cirrhosis

BACKGROUND/AIMS: The activation pathway of hepatocyte growth factor (HGF), including HGF activator (HGFA) and HGFA inhibitor-1, 2 (HAI-1, 2), has recently been clarified. The present study examined mRNA expressions of HGF, HGFA and HAI-1 following partial hepatectomy in normal and cirrhotic rats. METHODOLOGY: Liver cirrhosis was induced by intraperitoneal injections of dimethylnitrosamine. Two weeks after, the cirrhotic and normal rats underwent 70% hepatectomy and the liver regeneration rate, DNA synthesis of hepatocytes, plasma HGF level, and mRNA expressions of HGF, HGFA, and HAI-1 in the liver, spleen, and lung were examined at different times. RESULTS: Liver regeneration in the cirrhotic rats was deteriorated with a later peak of hepatocellular DNA synthesis. Hepatic HGF mRNA and splenic HAI-1 mRNA were upregulated and liver HGFA mRNA was downregulated in the cirrhotic rats. CONCLUSIONS: Insufficient HGF activation both by a reduced expression of hepatic HGFA and an increased expression of splenic HAI-1 may be one of the reasons for the impaired liver regeneration in cirrhosis.     

Beneficial effects of splenectomy on massive hepatectomy model in rats

Aim:  Possible spleno-hepatic relationships during hepatectomy remain unclear. The purpose of this study was to investigate the impact of splenectomy during massive hepatectomy in rats.
Methods:  Rats were divided into the following two groups: 90% hepatectomy (Hx group), hepatectomy with splenectomy (Hx+Sp group). The following parameters were evaluated; survival rate, biochemical parameters, quantitative RT-PCR for hemeoxygenase-1 (HO-1) and tumor necrosing factor α (TNFα), immunohistochemical staining for HO-1, proliferating cell nuclear antigen labeling index and liver weights.
Results:  The survival rate after massive hepatectomy significantly improved in Hx+Sp group as well as serum biochemical parameters, compared with Hx group ( P  < 0.05). HO-1 positive hepatocytes and its mRNA expression significantly increased and TNFα mRNA expression significantly decreased in Hx+Sp group compared with Hx group ( P  < 0.05). Moreover, liver regeneration was significantly accelerated at 48 and 72 h after hepatectomy in Hx+Sp group.
Conclusions:  Splenectomy had beneficial effects on massive hepatectomy by ameliorating liver injuries and promoting preferable liver regeneration.     

Mild hypothermia does not affect liver regeneration after partial hepatectomy in mice

Background: The use of mild hypothermia has been suggested to be therapeutically useful in treating acute liver failure. It is not known if hypothermia influences liver regeneration. Aim: To assess the effect of hypothermia on liver regeneration in mice. Methods: After partial (70%) hepatectomy (PHx), C57BL6/J mice were randomly assigned to either a hypothermic group or a normothermic group. Controlled mild hypothermia was maintained for up to 3 h after surgery. In addition, assessment of liver mass restitution was examined by studying the induction of key cell cycle proteins (cyclin A, D1 and E) and hepatocyte proliferation [assessment of proliferating cell nuclear antigen (PCNA) protein expression] by Western blotting and DNA synthesis by measuring 5‐bromo‐2‐deoxyuridine (BrdU) incorporation by immunohistochemical techniques 45 h after PHx. Results: Partial hepatectomy induced a vigorous proliferative response in the remnant livers of both groups of mice (normothermic and hypothermic groups), as evidenced by the induction of key cyclins, PCNA and incorporation of BrdU after PHx. The liver/body weight ratio and both cyclin and PCNA protein expression as well as BrdU incorporation did not differ between the regenerating livers of hypothermic and normothermic groups. Conclusion: Mild hypothermia does not influence liver regeneration in mice.     

FK506 promotes liver regeneration by suppressing natural killer cell activity

We examined the mechanism of promotion of liver regeneration by tacrolimus hydrate (FK506), a potent immunosuppressant, after partial hepatectomy. The administration of FK506 significantly increased the bromodeoxyuridine (BrdU) labelling index at 36 and 48 h after 70% hepatectomy compared with the placebo group. Using the same model, we examined the effect of FK506 on the expression of hepatocyte growth factor (HGF) and transforming growth factor-β1 (TGF-β1) and found no changes in HGF and TGF-β1 mRNA expression in the liver or in the HGF protein concentration in plasma. We found that pretreatment with FK506 markedly reduced the activity and number of liver-resident natural killer (NK) cells at the time of partial hepatectomy. Our observations suggest that the promotion of liver regeneration by FK506 may be attributable to a reduction in the number of liver-resident NK cells and to inhibition of their activity.     

Expression of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 in normal and malignant tissues of gastrointestinal tract

AIM: To provide the expression profile of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 (HAI-1) in normal and malignant tissues of gastrointestinal tract at mRNA level for further study on their correlations with tumor progression and metastasis. METHODS: Total RNAs were prepared from 37 samples of colorectal cancer tissues, 40 samples of gastric cancer tissues, and their adjacent normal tissues. The expression of SNC19/matriptase and HAM in these samples was detected by real-time fluorescent quantitative PCR using glyceraldehyde-3-phosphate dehydrogenase as internal standard, and the clinical significance for the correlation with clinicopathological parameters was evaluated. RESULTS: In gastric cancer tissues the expression of HAI-1 and SNC19/matriptase was significantly lower than that in the corresponding adjacent normal tissues (Z=-3.280, P= 0.006; Z=-4.651, P=0.000). HAI-1:SNC19/matriptase ratio showed no difference between normal and malignant tissues (P>0.05). Analysis of clinicopathological parameters showed decreased expression of HAM and HAI-1:SNC19/ matriptase ratio associated with stage Ⅲ/Ⅳ gastric tumors as compared to stage Ⅰ/Ⅱ ones (Z = -2.140, P= 0.031; Z= -2.155, P= 0.031), and with lymph node-positive gastric cancer tissues as compared to lymph node-negative ones (Z= -2.081, P= 0.036; Z= -2.686, P= 0.006). The expression of SNC19/matriptase had no relationship with stages and lymph node metastasis (P>0.05). The expression of HAM and HAM:SNC19/matriptase ratio increased in well-differentiated gastric cancer tissues, but there was no statistical significance (P>0.05). The difference of SNC19/matriptase expression was not significant in gastric cancer tissues of different histological differentiation status (P>0.05). In colorectal cancer tissues, the expression of HAI-1 and SNC19/matriptase was also markedly lower than that in their adjacent normal tissues (Z=-3.100, P=0.002; Z=-2.731, P=0.006), whereas HAI-1:SNC19/matriptase ratio showed no difference. Decreased expression of HAI-1 was associated with increased invasive depth and lymph node metastasis, but there was no statistical significance (P>0.05). The difference of SNC19/matriptase expression and HAI-1: SNC19/matriptase ratio was not significant in different stages and different lymph node metastasis status (P>0.05). The expression of SNC19/matriptase, HAI-1 or HAI-1: SNC19/matriptase ratio showed no difference in colorectal cancer tissues of different histological differentiation status (P>0.05). CONCLUSION: The expressions of SNC19/matriptase and its inhibitor HAI-1 are decreased in gastrointestinal cancer tissues compared to their normal counterparts, and the decreased expression of HAI-1 may correlate with invasion and lymph node metastasis. The possible mechanisms involved need to be further investigated.     

Liver gene regulation in rats following both 70 or 90% hepatectomy and endotoxin treatment

BACKGROUND: The metabolic state effect of liver failure on liver gene regulation was evaluated in a rat model. METHODS: Following 70 or 90% hepatectomy and lipopolysaccharide or vehicle treatment at intervals up to 24 h, the liver remnants were analyzed for mRNA levels for acute-phase, liver-specific and growth-related proteins. RESULTS: After 70% hepatectomy mRNA for alpha 1-acid glycoprotein, alpha 2-macroglobulin, thiostatin and fibrinogen, haptoglobin increased three- to sevenfold (P < 0.05), and mRNA for cyclin D and histone 3 increased seven- and 15-fold (P < 0.05), respectively. After lipopolysaccharide injection and 70% hepatectomy were done, mRNA for acute-phase proteins raised significantly (P < 0.05), more to five to 20-fold, while mRNA for growth-related proteins raised significantly (P < 0.05) less to three- to fourfold. After 90% hepatectomy, acute-phase protein mRNA increased five- to ninefold (P < 0.05) more than after 70% hepatectomy, while mRNA for histone 3 and cyclin D did not increase within 24 h, which indicates a delayed growth after 90% hepatectomy. In 90% of hepatectomized rats treated with lipopolysaccharide, acute-phase protein mRNA raised three- to sixfold (P < 0.05) less than after vehicle treatment. CONCLUSION: In endotoxemia from liver failure, the synthesis of acute-phase proteins is upregulated by gene regulation at the expense of that for regeneration, which may be an appropriate response for immediate survival. In severe liver failure, endotoxin may interfere with the appropriate gene regulation.     

缺氧诱导因子α亚型基因在急性心肌梗死大鼠缺血心肌表达的变化

目的 通过观察急性心肌梗死(AMI)大鼠心肌缺氧诱导因子 (hypoia-inducible factor,HIF) 3个α亚型mRNA表达的动态变化,探讨其在早期缺血心肌中的作用.方法 将大鼠随机分为对照组和AMI组.用HE染色观察心肌形态学变化, RT-PCR检测术后1、2、4、6、12 h缺血心肌HIF 3个α亚型mRNA表达情况.结果 HIF-1α、2α、3α mRNA在正常心肌中均有表达.术后1 h,缺血心肌HIF-1α mRNA表达明显上调(P<0.05),2 h达高峰(P<0.01),4 h开始下降(P＜0.05),6 h降至正常水平,12 h维持在正常水平;HIF-2α、3α mRNA在急性缺血心肌表达无明显变化.结论 早期急性心肌缺血可诱导HIF-1α基因表达改变,与HIF-2α、3α基因表达无关.